This proposal seeks to discover a steroid for adjunctive treatment of androgen-dependent prostatic carcinoma which will act by interfering with dihydrotestosterone economy at the enzyme and receptor levels. To this end, steroids designed as 5 alpha-reductase inhibitors and as androgen-receptor antagonists, respectively, will be synthesized. These compounds will then be studied biologically in tissue-culture models including human prostatic cancer preparations. In this way it is hoped that activity data relevant to the human disease will be obtained. In addition, the products will be screened in a preliminary manner for 5 alpha-reductase inhibition, dihydrotestosterone-receptor binding affinity and anti-androgenic activity. The more active structures will be used as leads to develop molecules incorporating the desirable features of both enzyme-inhibitors and receptor antagonists for detailed biological evaluation.